Ayrton Roberto Massaro

Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF

BACKGROUND In ROCKET AF, rivaroxaban was non-inferior to adjusted-dose warfarin in preventing stroke or systemic embolism among patients with atrial fibrillation (AF). We aimed to investigate whether the efficacy and safety of rivaroxaban compared with warfarin is consistent among the subgroups of patients with and without previous stroke or transient ischaemic attack (TIA). METHODS In ROCKET AF, patients with AF who were at increased risk of stroke were randomly assigned (1:1) in a double-blind manner to rivaroxaban 20 mg daily or adjusted dose warfarin (international normalised ratio 2·0-3·0). Patients and investigators were masked to treatment allocation. Between Dec 18, 2006, and June 17, 2009, 14 264 patients from 1178 centres in 45 countries were randomly assigned. The primary endpoint was the composite of stroke or non-CNS systemic embolism. In this substudy we assessed the interaction of the treatment effects of rivaroxaban and warfarin among patients with and without previous stroke or TIA. Efficacy analyses were by intention to treat and safety analyses were done in the on-treatment population. ROCKET AF is registered with ClinicalTrials.gov, number NCT00403767. FINDINGS 7468 (52%) patients had a previous stroke (n=4907) or TIA (n=2561) and 6796 (48%) had no previous stroke or TIA. The number of events per 100 person-years for the primary endpoint in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (2·79% rivaroxaban vs 2·96% warfarin; hazard ratio [HR] 0·94, 95% CI 0·77-1·16) and those without (1·44%vs 1·88%; 0·77, 0·58-1·01; interaction p=0·23). The number of major and non-major clinically relevant bleeding events per 100 person-years in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (13·31% rivaroxaban vs 13·87% warfarin; HR 0·96, 95% CI 0·87-1·07) and those without (16·69%vs 15·19%; 1·10, 0·99-1·21; interaction p=0·08). INTERPRETATION There was no evidence that the relative efficacy and safety of rivaroxaban compared with warfarin was different between patients who had a previous stroke or TIA and those who had no previous stroke or TIA. These results support the use of rivaroxaban as an alternative to warfarin for prevention of recurrent as well as initial stroke in patients with AF. FUNDING Johnson and Johnson Pharmaceutical Research and Development and Bayer HealthCare.

European Stroke Initiative Recommendations for Stroke Management

This article summarises recommendations for acute management of stroke by the European Stroke Initiative (EUSI), on behalf of the European Stroke Council (ESC), the European Neurological Society (ENS), and the European Federation of Neurological Societies (EFNS).

Stroke Awareness in Brazil Alarming Results in a Community-Based Study

Background and Purpose— Stroke is the leading cause of death in Brazil. This community-based study assessed lay knowledge about stroke recognition and treatment and risk factors for cerebrovascular diseases and activation of emergency medical services in Brazil. Methods— The study was conducted between July 2004 and December 2005. Subjects were selected from the urban population in transit about public places of 4 major Brazilian cities: São Paulo, Salvador, Fortaleza, and Ribeirão Preto. Trained medical students, residents, and neurologists interviewed subjects using a structured, open-ended questionnaire in Portuguese based on a case presentation of a typical patient with acute stroke at home. Results— Eight hundred fourteen subjects were interviewed during the study period (53.9% women; mean age, 39.2 years; age range, 18 to 80 years). There were 28 different Portuguese terms to name stroke. Twenty-two percent did not recognize any warning signs of stroke. Only 34.6% of subjects answered the correct nationwide emergency telephone number in Brazil (#192). Only 51.4% of subjects would call emergency medical services for a relative with symptoms of stroke. In a multivariate analysis, individuals with higher education called emergency medical services (P=0.038, OR=1.5, 95%, CI: 1.02 to 2.2) and knew at least one risk factor for stroke (P<0.05, OR=2.0, 95% CI: 1.2 to 3.2) more often than those with lower education. Conclusions— Our study discloses alarming lack of knowledge about activation of emergency medical services and availability of acute stroke treatment in Brazil. These findings have implications for public health initiatives in the treatment of stroke and other cardiovascular emergencies.

Clinical discriminators of lobar and deep hemorrhages: The Stroke Data Bank

Of the 1,805 patients with acute stroke enrolled in the Stroke Data Bank, 237 had parenchymatous hemorrhage. After excluding 34 secondary intracerebral and 31 infratentorial hemorrhage patients, a logistic regression analysis of the 172 patients with primary supratentorial intracerebral hemorrhage (ICH) elucidated clinical factors that distinguished the 65 patients with lobar hemorrhage (LH) from the 107 patients with deep hemorrhage (DH) located in the basal ganglia and thalamus. In LH, severe headache was more common than in DH, while hypertension and motor deficit were significantly less common. Patients with either LH or DH had a similar prognosis and mean Glasgow Coma Scale (GCS) scores, despite the hematoma volume measured on the the initial CT being significantly greater for LH than DH. The presence of intraventricular extension (IVH) was more frequent in DH. The frequency of IVH increased with hematoma volume in LH, but remained constant for DH. Two CT variables (IVH and hematoma volume) that differed in these two hemorrhage groups were important predictors of coma (GCS ±8) in a logistic regression model. Differences in the frequency of IVH may help explain why the degree of impairment in consciousness was similar in the two groups. Among patients with supratentorial ICH, location of the hematoma is related to both volume and IVH, which are important determinants of the level of consciousness.

Delay in the Diagnosis of Cerebral Vein and Dural Sinus Thrombosis: Influence on Outcome

Background and Purpose— Diagnostic delay of cerebral vein and dural sinus thrombosis may have an impact on outcome. Methods— In the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) cohort (624 patients with cerebral vein and dural sinus thrombosis), we analyzed the predictors and the impact on outcome of diagnostic delay. Primary outcome was a modified Rankin Scale score >2 at the end of follow-up. Secondary outcomes were modified Rankin Scale score 0 to 1 at the end of follow-up, death, and visual deficits (visual acuity or visual field). Results— Median delay was 7 days (interquartile range, 3 to 16). Patients with disturbance of consciousness (P<0.001) and of mental status (P=0.042), seizure (<0.001), and with parenchymal lesions on admission CT/MR (P<0.001) were diagnosed earlier, whereas men (P=0.01) and those with isolated intracranial hypertension syndrome (P=0.04) were diagnosed later. Between patients diagnosed earlier and later than the median delay, no statistically significant differences were found in the primary (P=0.33) and in secondary outcomes: modified Rankin Scale score 0 to 1 (P=0.86) or deaths (P=0.53). Persistent visual deficits were more frequent in patients diagnosed later (P=0.05). In patients with isolated intracranial hypertension syndrome, modified Rankin Scale score >2 at the end of follow-up was more frequent in patients diagnosed later (P=0.02). Conclusions— Diagnostic delay was considerable in this cohort and was associated with an increased risk of visual deficit. In patients with isolated intracranial hypertension syndrome, diagnostic delay was also associated with death or dependency.

Transcranial Doppler assessment of cerebral blood flow: Effect of cardiac transplantation

The authors prospectively studied transcranial Doppler changes in patients with refractory congestive heart failure before and after cardiac transplantation. They evaluated 22 patients preoperatively and 14 patients after transplantation. Mean postoperative flow velocity increased by 53.3% (p < 0.0001). Preoperative waveform changes became normal after transplantation.

Acute treatment costs of stroke in Brazil.

Background and Purpose: Although stroke is the leading cause of death in Brazil, little information exist on the acute treatment provided for stroke and its associated costs. This study addresses this gap by both clinically and economically characterizing the acute treatment of first-ever intracerebral hemorrhage (ICH) and ischemic stroke (IS) in Brazil. Methods: Retrospective medical chart review using data from two high-volume stroke centers in São Paulo, Brazil. Clinical and resource utilization data for all patients admitted to the stroke centers with a first-ever stroke between January 1, 2006 and May 31, 2007 were collected and the mean acute treatment costs per person were calculated by assigning appropriate unit cost data to all resource use. Cost estimates in Brazilian reals (BRL) were converted to US dollars (USD) using the 2005 purchasing power parity index. National costs of acute treatment for incident strokes were estimated by extrapolation of mean cost estimate per person to national incidence data for the two types of stroke. The mean costs of acute treatment on a national scale were examined in sensitivity analysis. Results: A total of 316 stroke patients were identified and their demographic and clinical characteristics, patterns of care, and outcomes were examined. Mean length of hospital stay was 12.0 ± 8.8 days for ICH and 13.3 ±23.4 days for IS. Ninety-one percent of the ICH patients and 68% of the IS patients were admitted to an intensive care unit (ICU). Mean total costs of initial hospitalization were USD 4,101 (SD ±4,254) for ICH and USD 1,902 (SD ±1,426) for IS. In multivariate analysis, hemorrhagic stroke, development of pneumonia, neurosurgical intervention, stay in ICU, and physical therapy were all significant independent predictors of acute treatment costs. Aggregate national health care expenditures for acute treatment of incident ICH were USD 122.4 million (range 30.8–274.2) and USD 326.9 million for IS (range 82.4–732.2). Conclusion: Acute treatment costs of incident ICH and IS in Brazil are substantial and primarily driven by the intensity of hospital treatment and in-hospital complications. With the expected increase in the incidence of stroke in Brazil over the coming decades, these results emphasize the need for effective preventive and acute medical care.

Transcranial Doppler ultrasonographic changes after treatment for arteriovenous malformations.

We performed transcranial Doppler ultrasonography on 15 patients with arteriovenous malformations before and after embolization or surgical resection to compare quantitatively the hemodynamic effects of these two treatments. Changes in mean blood velocity and pulsatility index were analyzed in 19 treated feeding arteries. Blood velocity decreased by a mean of 38.1% or 46.5 cm/sec (p less than 0.0001, two-tailed paired t test); decreases were greater for surgically resected arteries (46.2% or 55.9 cm/sec, p less than 0.003) than for embolized arteries (30.8% or 38.0 cm/sec, p less than 0.0003). Pulsatility index increased by a mean of 54.7% or 0.25 (p = 0.0001); increases were greater for surgically resected arteries (65.8% or 0.29, p = 0.0045) than for embolized arteries (44.8% or 0.20, p less than 0.001). The differences in the changes in blood velocity and pulsatility index between treatment groups were not significant. These data demonstrate that embolization results in hemodynamic changes that are qualitatively similar to those occurring after surgical resection of arteriovenous malformations. Transcranial Doppler ultrasonography is a reliable and convenient noninvasive method for monitoring hemodynamic effects of treatments for arteriovenous malformations.

Risk score to predict the outcome of patients with cerebral vein and dural sinus thrombosis.

Background: Around 15% of patients die or become dependent after cerebral vein and dural sinus thrombosis (CVT). Method: We used the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) sample (624 patients, with a median follow-up time of 478 days) to develop a Cox proportional hazards regression model to predict outcome, dichotomised by a modified Rankin Scale score >2. From the model hazard ratios, a risk score was derived and a cut-off point selected. The model and the score were tested in 2 validation samples: (1) the prospective Cerebral Venous Thrombosis Portuguese Collaborative Study Group (VENOPORT) sample with 91 patients; (2) a sample of 169 consecutive CVT patients admitted to 5 ISCVT centres after the end of the ISCVT recruitment period. Sensitivity, specificity, c statistics and overall efficiency to predict outcome at 6 months were calculated. Results: The model (hazard ratios: malignancy 4.53; coma 4.19; thrombosis of the deep venous system 3.03; mental status disturbance 2.18; male gender 1.60; intracranial haemorrhage 1.42) had overall efficiencies of 85.1, 84.4 and 90.0%, in the derivation sample and validation samples 1 and 2, respectively. Using the risk score (range from 0 to 9) with a cut-off of ≥3 points, overall efficiency was 85.4, 84.4 and 90.1% in the derivation sample and validation samples 1 and 2, respectively. Sensitivity and specificity in the combined samples were 96.1 and 13.6%, respectively. Conclusions: The CVT risk score has a good estimated overall rate of correct classifications in both validation samples, but its specificity is low. It can be used to avoid unnecessary or dangerous interventions in low-risk patients, and may help to identify high-risk CVT patients.

Transcranial Doppler ultrasonography in adults with sickle cell disease

Background: Transcranial Doppler (TCD) is used to select children with sickle cell disease (SCD) for primary stroke prevention using regular blood transfusion. Whether it can also identify high stroke risk in adults with SCD is not known. Methods: The authors examined 112 adult patients from two convenience population samples with SCD and 53 healthy control subjects to compare velocities in adults to those reported in children with SCD and to evaluate the influence of age and hematocrit on TCD. Results: Adults with SCD had a higher mean time-averaged maximum mean velocity (110.9 ± 25.7 cm/s) compared with healthy controls (71.1 ± 12.0 cm/s), and the difference is approximately proportional to their anemia. No cases with velocities ≥200 cm/s (the threshold used in children for prophylactic treatment) were found in this sample. Conclusions: Transcranial Doppler velocities in adults with sickle cell disease (SCD) are lower than those in children with SCD. Velocity criteria used in children cannot be used to stratify risk of stroke in adults.